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Phenotypic alterations in liver cancer cells induced by mechanochemical disruption
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis worldwide. Currently, no curative treatment is available for early-to-intermediate stage HCC, characterized by large and/or multifocal tumors. If left untreated, HCC rapidly progresses to a lethal stage due to favorable conditions for metastatic spread. Mechanochemical disruption of cellular structures can potentially induce phenotypic alterations in surviving tumor cells that prevent HCC progression. In this paper, HCC response to mechanical vibration via high-intensity focused ultrasound and a chemical disruptive agent (ethanol) was examined in vitro and in vivo. Our analysis revealed that mechanochemical disruption caused a significant overproduction of reactive oxygen species (ROS) in multiple HCC cell lines (HepG2, PLC/PRF/5, and Hep3B). This led to a decrease in cell viability and long-term proliferation due to increased expression and activity of death receptors TNFR1 and Fas. The cells that survived mechanochemical disruption had a reduced expression of cancer stem cell markers (CD133, CD90, CD49f) and a diminished colony-forming ability. Mechanochemical disruption also impeded HCC migration and their adhesion to vascular endothelium, two critical processes in hematogenous metastasis. The HCC transformation to a non-tumorigenic phenotype post mechanochemical disruption was confirmed by a lack of tumor spheroid formation in vitro and complete tumor regression in vivo. These results show that mechanochemical disruption inhibits uncontrolled proliferation and reduces tumorigenicity and aggressiveness of HCC cells through ROS overproduction and associated activation of TNF- and Fas-mediated cell death signaling. Our study identifies a novel curative therapeutic approach that can prevent the development of aggressive HCC phenotypes.
- Subjects :
- Male
0301 basic medicine
Carcinoma, Hepatocellular
Cancer therapy
Hepatocellular carcinoma
Cell Survival
lcsh:Medicine
Apoptosis
Integrin alpha6
Article
Mice
03 medical and health sciences
0302 clinical medicine
Cancer stem cell
In vivo
Cell Line, Tumor
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
CD90
AC133 Antigen
fas Receptor
lcsh:Science
Cell Proliferation
chemistry.chemical_classification
Reactive oxygen species
Multidisciplinary
business.industry
lcsh:R
Liver Neoplasms
Hep G2 Cells
medicine.disease
digestive system diseases
030104 developmental biology
chemistry
Receptors, Tumor Necrosis Factor, Type I
Cell culture
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Cancer research
Thy-1 Antigens
lcsh:Q
Female
Tumor necrosis factor alpha
Reactive Oxygen Species
Liver cancer
business
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....85f94f005a02980526f84c9209b58ea8